rs4491689

chr2-26417913-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145038.5(DRC1):c.244-3375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,206 control chromosomes in the GnomAD database, including 59,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (59108 hom., cov: 31)
• Consequence: DRC1 NM_145038.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

Genes affected

DRC1 (HGNC:24245): (dynein regulatory complex subunit 1) This gene encodes a central component of the nexin-dynein complex (N-DRC), which regulates the assembly of ciliary dynein. Mutations in this gene can cause ciliary dyskinesia. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRC1	NM_145038.5	c.244-3375G>A		intron_variant		ENST00000288710.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7	c.244-3375G>A		intron_variant		2	NM_145038.5	P1
DRC1	ENST00000421869.5	c.244-3375G>A		intron_variant, NMD_transcript_variant		1
DRC1	ENST00000649059.1	c.230-3375G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132731 AN: 152086 Hom.: 59071 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.869

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.873 AC: 132825 AN: 152206 Hom.: 59108 Cov.: 31 AF XY: 0.867 AC XY: 64525 AN XY: 74430

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.874

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.949

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.869

Alfa AF: 0.908 Hom.: 124041

Bravo AF: 0.854

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.6
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4491689; hg19: chr2-26640781;